title: An update on the oxygen stress-mitochondrial mutation theory of aging: genetic and evolutionary implications.
abstract: The acceleration of fixed-postmitotic cell aging by a high metabolic rate and the age related loss of mitochondria found in that cell type led us to propose an oxygen stress-mitochondrial mutation theory of aging, according to which senescence may be linked to mutations of the mitochondrial genome (mtDNA) of the irreversibly differentiated cells. This extranuclear somatic gene mutation concept of aging is supported by the fact that mtDNA synthesis takes place at the inner mitochondrial membrane near the sites of formation of highly reactive oxygen species. Mitochondrial DNA may be unable to prevent the intrinsic mutagenesis caused by those byproducts of respiration because, in contrast to the nuclear genome, it lacks excision and recombination repair. The resulting mitochondrial impairment and concomitant cell bioenergetic decline may cause the senescent loss of physiological performance and may play a key role in the pathogenesis of many age-related degenerative diseases. These concepts are integrated with classic and contemporary hypotheses in a unitary theory that reconciles programmed and stochastic concepts of aging. Thus, it is suggested that cells are programmed to differentiate, and then they accumulate mitochondrial-genetic damage because of their high levels of oxyradical stress and the loss of the organelle rejuvenating power of mitosis.
authors.affiliation: Instituto de Neurociencias, Facultad de Medicina, Alicante, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Miquel
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D005075:Biological Evolution; D004272:DNA, Mitochondrial / Q000235:genetics*; D004330:Drosophila / Q000235:genetics; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D013269:Stochastic Processes
chemical_list: D004272:DNA, Mitochondrial